TAA Specific Cytotoxic T Lymphocytes in Patients With Breast Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 2/14/2019 |
| Start Date: | October 10, 2017 |
| End Date: | November 1, 2024 |
| Contact: | Mothaffar F Rimawi, MD |
| Email: | rimawi@bcm.tmc.edu |
| Phone: | 713-798-1311 |
Tumor Associated Antigen (TAA) Specific Cytotoxic T Lymphocytes Administered in Patients With Breast Cancer
The study is being conducted in patients in which breast cancer has come back after standard
treatment. Volunteers in this research study are treated using special immune system cells
called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental
therapy.
The proteins that investigators are targeting in this study are called tumor-associated
antigens (TAAs). These are cell proteins that are specific to the cancer cell. They do not
show, or they show up in low quantities, on normal human cells. In this study, investigators
target five common TAAs. They are called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX2. On a
different study, patients have been treated and so far this treatment has shown to be safe.
Investigators now want to try this treatment in patients with breast cancer.
These TAA-specific cytotoxic T lymphocytes (TAA-CTLs) are an investigational product not
approved by the Food and Drug Administration.
The purpose of this study is to determine the clinical efficacy of TAA-specific CTLs, to
learn what the side-effects are, and to see whether this therapy might help patients with
breast cancer.
treatment. Volunteers in this research study are treated using special immune system cells
called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental
therapy.
The proteins that investigators are targeting in this study are called tumor-associated
antigens (TAAs). These are cell proteins that are specific to the cancer cell. They do not
show, or they show up in low quantities, on normal human cells. In this study, investigators
target five common TAAs. They are called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX2. On a
different study, patients have been treated and so far this treatment has shown to be safe.
Investigators now want to try this treatment in patients with breast cancer.
These TAA-specific cytotoxic T lymphocytes (TAA-CTLs) are an investigational product not
approved by the Food and Drug Administration.
The purpose of this study is to determine the clinical efficacy of TAA-specific CTLs, to
learn what the side-effects are, and to see whether this therapy might help patients with
breast cancer.
Investigators will take a maximum of approximately 79 teaspoons of blood from patients on one
to three occasions over a two-month period. Under certain conditions related to the patient's
health, blood may be collected using a process called apheresis. Apheresis is the process
where blood is passed through a machine that separates out the components of blood that we
need. The remainder of the patient's blood will then be returned to his/her body.
Investigators will use this blood to grow T cells. Investigators will first grow a special
type of cells called dendritic cells which will activate T cells. Once these are made,
investigators will load them with small pieces of protein called peptides taken from the TAAs
that we want to target. This helps train the T cells to kill cancer cells which express TAAs
on their surface. Then the TAA-specific CTLs are expanded.
The cells will be infused by intravenous infusion (IV) into the patient over 1-10 minutes.
The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl).
Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible
allergic reaction to the TAA-CTL administration. Initially, two doses of TAA-CTLs will be
given four weeks apart. The patient's cancer will be assessed pre-infusion, and then 6 weeks
after the second infusion. If after the second infusion there is a reduction in the size of
the patient's tumor on Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or
Positron Emission Tomography (PET) as assessed by a radiologist, the patient can receive up
to six (6) additional doses of the TAA-CTLs if they wish. At least one month should pass
before each additional dose. All of the treatments will be given by the Center for Cell and
Gene Therapy at Houston Methodist Hospital.
In between the first and second TAA-CTL infusions, and for 6 weeks after the 2nd infusion,
the patient should not receive any other anti-cancer treatments such as radiation therapy or
chemotherapy. If the patient does receive any other therapies in-between the first and second
infusion of TAA-CTLs, they will be taken off treatment and will not be able to receive the
second infusion.
MEDICAL TESTS BEFORE TREATMENT:
Before being treated, patients will receive a series of standard medical tests:
- Physical exam.
- Blood tests to measure blood cells, kidney and liver function.
- Measurements of the patient's tumor by routine imaging studies.
- Pregnancy test if the patient is a female who can have children.
MEDICAL TESTS DURING TREATMENT:
Patients will receive standard medical tests on the day of their second and subsequent
infusions:
- Physical exam
- Blood tests to measure blood cells, kidney and liver function.
MEDICAL TESTS AFTER TREATMENT
- Imaging study 6 weeks after the 2nd TAA-CTL infusion.
To learn more about the way the TAA-CTLs are working in the patient's body, an extra 20-40 mL
(4-8 teaspoons) of blood will be taken before each infusion, at Weeks 1, 2, and 4 after the
first cell dose and at Weeks 1, 2, 4 and 6 after the second cell dose. Afterwards, blood will
be collected at 3, 6, 9 and 12 months after the 2nd infusion. Investigators will use this
blood to see how long the TAA-CTLs last, and to look at the patient's immune system response
to the cancer. The immune system is part of the body that helps protect against disease.
Study Duration: The patient's active participation in this study will last for approximately
one (1) year. If the patient receives additional doses of the TAA-CTLs as described above,
his/her active participation will last until one (1) year after the last dose. Investigators
will then contact the patient once a year for up to 4 additional years (total of 5 years
follow-up) in order to evaluate the patient's disease response long-term.
to three occasions over a two-month period. Under certain conditions related to the patient's
health, blood may be collected using a process called apheresis. Apheresis is the process
where blood is passed through a machine that separates out the components of blood that we
need. The remainder of the patient's blood will then be returned to his/her body.
Investigators will use this blood to grow T cells. Investigators will first grow a special
type of cells called dendritic cells which will activate T cells. Once these are made,
investigators will load them with small pieces of protein called peptides taken from the TAAs
that we want to target. This helps train the T cells to kill cancer cells which express TAAs
on their surface. Then the TAA-specific CTLs are expanded.
The cells will be infused by intravenous infusion (IV) into the patient over 1-10 minutes.
The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl).
Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible
allergic reaction to the TAA-CTL administration. Initially, two doses of TAA-CTLs will be
given four weeks apart. The patient's cancer will be assessed pre-infusion, and then 6 weeks
after the second infusion. If after the second infusion there is a reduction in the size of
the patient's tumor on Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or
Positron Emission Tomography (PET) as assessed by a radiologist, the patient can receive up
to six (6) additional doses of the TAA-CTLs if they wish. At least one month should pass
before each additional dose. All of the treatments will be given by the Center for Cell and
Gene Therapy at Houston Methodist Hospital.
In between the first and second TAA-CTL infusions, and for 6 weeks after the 2nd infusion,
the patient should not receive any other anti-cancer treatments such as radiation therapy or
chemotherapy. If the patient does receive any other therapies in-between the first and second
infusion of TAA-CTLs, they will be taken off treatment and will not be able to receive the
second infusion.
MEDICAL TESTS BEFORE TREATMENT:
Before being treated, patients will receive a series of standard medical tests:
- Physical exam.
- Blood tests to measure blood cells, kidney and liver function.
- Measurements of the patient's tumor by routine imaging studies.
- Pregnancy test if the patient is a female who can have children.
MEDICAL TESTS DURING TREATMENT:
Patients will receive standard medical tests on the day of their second and subsequent
infusions:
- Physical exam
- Blood tests to measure blood cells, kidney and liver function.
MEDICAL TESTS AFTER TREATMENT
- Imaging study 6 weeks after the 2nd TAA-CTL infusion.
To learn more about the way the TAA-CTLs are working in the patient's body, an extra 20-40 mL
(4-8 teaspoons) of blood will be taken before each infusion, at Weeks 1, 2, and 4 after the
first cell dose and at Weeks 1, 2, 4 and 6 after the second cell dose. Afterwards, blood will
be collected at 3, 6, 9 and 12 months after the 2nd infusion. Investigators will use this
blood to see how long the TAA-CTLs last, and to look at the patient's immune system response
to the cancer. The immune system is part of the body that helps protect against disease.
Study Duration: The patient's active participation in this study will last for approximately
one (1) year. If the patient receives additional doses of the TAA-CTLs as described above,
his/her active participation will last until one (1) year after the last dose. Investigators
will then contact the patient once a year for up to 4 additional years (total of 5 years
follow-up) in order to evaluate the patient's disease response long-term.
PROCUREMENT INCLUSION CRITERIA:
1. Any breast cancer patient with metastatic or locally recurrent unresectable disease.
2. Patients with life expectancy greater than or equal to 12 weeks.
3. Age greater than or equal to 18 and less than or equal to 80 years old.
4. Hgb greater than 8.0.
5. Informed Consent explained to, understood by and signed by patient. Patient given copy
of informed consent.
TREATMENT INCLUSION CRITERIA:
1. Any breast cancer patient with metastatic or locally recurrent unresectable breast
cancer currently progressive, after at least two prior lines of therapy in the
advanced setting. Patients with HER2+ disease must have failed two or more different
anti-HER2 agents.
2. Patients must have measurable or evaluable disease per RECIST 1.1 criteria.
3. Patients with life expectancy greater than or equal to 12 weeks.
4. Age greater than or equal to 18 and less than or equal to 80 years old.
5. Pulse oximetry of greater than 95% on room air.
6. Patients with ECOG score less than or equal to 2 or a Karnofsky score of greater than
or equal to 50.
7. Patients with bilirubin less than or equal to 2x upper limit of normal, AST less than
or equal to 3x upper limit of normal, and Hgb greater than 8.0.
8. Patients with a creatinine normal for age.
9. Patients should have been off other investigational therapy for one month prior to
receiving treatment on this study.
10. Patients should have been off conventional therapy for at least 1 week prior to
receiving treatment on this study.
11. Sexually active patients must be willing to utilize one of the more effective birth
control methods for 6 months after the T cell infusion.
12. Informed Consent explained to, understood by and signed by patient. Patient given copy
of informed consent.
PROCUREMENT EXCLUSION CRITERIA:
1. Patients with severe intercurrent infection.
2. Patients with active HIV infection at time of procurement.
3. Patients with a chronic uncontrolled medical condition that, in the opinion of the
principal investigator, precludes them from participation.
TREATMENT EXCLUSION CRITERIA:
1. Patients with severe intercurrent infection.
2. Patients receiving systemic corticosteroids (Patients off steroids for at least 48
hours are eligible).
3. Pregnant or lactating.
4. Patients with a chronic uncontrolled medical condition that, in the opinion of the
principal investigator, precludes them from participation.
5. HIV positive.
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